Rv2022c Family assigned · medium auto-curated
H37Rv Rv2022c · MTBC0 mtbc0_002152 ·
201 aa · 2290732–2291337 (-) ·
RefSeq NP_216538.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | type II toxin-antitoxin system RelE/ParE family toxin |
| Revised (this work) | Type II toxin-antitoxin system RelE/ParE family toxin. Pfam: Gp49 (PF05973.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53468
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Putative toxin HigB2 |
| Curated function | Putative toxic component of a type II toxin-antitoxin (TA) system. Its cognate antitoxin would be HigA2. |
UniProt still lists this protein as Putative toxin HigB2; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Phage derived protein Gp49-like (DUF891) |
| Orthologous group | COG4683 |
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.852 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 11 missense, 0 nonsense, 0 frameshift |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Gp49 | PF05973.21 | 1.2e-20 | 87–181 | Phage derived protein Gp49-like (DUF891) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: higA2 (transcriptional regulator), high confidence from genomic context alone (score 981 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2021c higA2 |
transcriptional regulator | 998 | 981 ctx | neighborhood:786 fusion:648 cooccurence:771 textmining:912 |
Rv3183 higA3 |
transcriptional regulator | 927 | 800 ctx | cooccurence:773 textmining:651 |
Rv2023c hyp |
hypothetical protein | 713 | 713 ctx | neighborhood:711 |
Rv2020c |
Rv2020c, (MTV018.07c), len: 99 aa. Conserved hypothetical protein, nearly identical to C-terminal part of hypothetical protein RvD1-Rv2024c' | 565 | 564 ctx | neighborhood:558 |
Rv1956 higA |
antitoxin HigA | 784 | 252 | textmining:724 |
Rv3384c vapC46 |
ribonuclease VapC46 | 673 | 177 | textmining:620 |
Rv3750c vapB50 |
excisionase | 607 | 170 | textmining:547 |
Rv2866 relG |
toxin RelG | 454 | 169 | |
Rv2865 relF |
antitoxin RelF | 510 | 167 | textmining:436 |
Rv0918 hyp |
hypothetical protein | 504 | 160 | textmining:434 |
Rv3749c vapC50 hyp |
hypothetical protein | 693 | 157 | textmining:651 |
Rv0065 vapC1 |
ribonuclease VapC1 | 501 | 153 | textmining:436 |
Rv0268c hyp |
hypothetical protein | 541 | 59 | textmining:533 |
Rv3188 hyp |
hypothetical protein | 445 | 55 | textmining:437 |
Rv1955 higB |
toxin HigB | 809 | 52 | textmining:807 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: type II toxin-antitoxin system RelE/ParE family toxin
- Pfam (hmmscan --cut_ga): Gp49 PF05973.21 (E=1e-20)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_216538.1)
- Domains: Pfam-A via hmmscan --cut_ga — Gp49 (PF05973.21)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG4683 - Curated reference: UniProt O53468 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
27 functional partner(s); context anchor
higA2 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002152|Rv2022c| MNVPWENAHGGALYCLIRGDEFSAWHRLLFQRPGCAESVLACRHFLDGSPVARCSYPEEYHPCVISRIALLCDSVGWTADVERISAWLNGLDRETYELVFAAIEVLEEEGPALGCPLVDTVRGSRHKNMKELRPGSQGRSEVRILFAFDPARQAIMLAAGNKAGRWTQWYDEKIKAADEMFAEHLAQFEDTKPKRRKRKKG